CURRICULUM VITÆ
`RODOLFO PINAL, Ph.D.
`
`Purdue University
`Department of Industrial and Physical Pharmacy
`575 Stadium Mall Drive
`West Lafayette, IN 47907
`+1-765-496-6247
`rpinal@purdue.edu
`
`EXPERIENCE:
`2009-Present
`2003-2009
`Department of Industrial and
`Physical Pharmacy
`Purdue University
`
`Associate Professor
`Assistant Professor
`
`Research:
`Leading and conducting graduate level research in the study of some of the most prevalent problems
`encountered during pharmaceutical product development, such as solubility, solubilization and drug delivery,
`from the theoretical framework provided by the properties of liquid (fluid and amorphous) mixtures. Drug-
`polymer and drug-lipid mixtures as systems for improved solubility, dissolution and drug delivery are among
`current research projects.
`
`Solubility, solubilization and drug delivery of liquid mixtures and amorphous systems
` Methods for enhancing oral bioavailability of poorly soluble active compounds
` Relationship between chemical structure and physical properties responsible for the solubility of
`drugs
` Development of amorphous formulations with improved drug solubility
`Stabilization of amorphous formulations through the study, modeling and control of molecular
`
`mobility
`
`Study of polymeric excipients and their interactions in pharmaceutical systems
`Investigation of the effect of polymer-plasticizer interactions on the mechanical and mass
`
`transport properties of pharmaceutical polymers
` Dispersions of drug microparticles in polymeric films as drug delivery systems
`Production of spatially dispersed, stable nanocrystals for delivery of highly insoluble anticancer
`
`drugs via transcytosis
` Development of polymeric strip films containing immobilized, spatially disperse API micro- and
`nano-particles
`
`Pharmaceutical Processing
`Influence of excipient raw material physical properties on the quality attributes products made by
`
`roller compaction
` Use of acoustic emission for the continuous monitoring and control of pharmaceutical
`manufacturing processes
` Matrix assisted co-crystallization (MAC). Use of hot-melt extrusion for the production of
`formulated co-crystals in a scalable/continuous process
`
`1
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 1 of 25
`
`

`

`Prefabricated (modular) dosage forms
` Guide the development of a new technology for the design and manufacture of pharmaceutical
`dosage forms
` Research and development on working parts based on desired function (ID/anti-counterfeiting,
`solubilization, crystallization inhibition, chemical stabilization, etc.)
`Blueprint design and 3D assembly of integrated dosage forms prototypes
`
` Comparative performance testing against commercial benchmark products
`
`International Activities:
`
`2013- Present. Visiting Professor, Shenyang Pharmaceutical University, Shenyang, China
`Teach general aspects of pharmaceutics and physical characterization of solids to graduate and
`
`undergraduate students
`Teach theoretical and formulation aspects of solubility and solubilization of drugs
`
` Cover physical characterization of pharmaceutical solids in training courses designed for industrial
`scientists working in the Chinese pharmaceutical industry
`Serve as co-advisor of Masters’ and Ph.D. students in the department of Pharmaceutics
`
`
`
`2014 – Summer Faculty on Pharmaceutical Technology, Universidad de Los Andes, Bogota, Colombia.
`Solubility, solubilization and drug release from liquid mixtures and amorphous systems.
`
`
`2015 - Present. Graduate thesis evaluation committee. Faculty of Pharmacy. Universidad Nacional de
`Colombia, Bogota, Colombia.
`Serve in graduate examination committee and thesis oral defense
`
`
`Teaching:
`
`Teaching of undergraduate and graduate level courses on Pharmaceutics, Pharmaceutical Technology and
`Drug Delivery. Specific teaching assignment of Sterile Products, a required course for senior pharmacy
`students.
`
`Code
`
`Course
`
`Role
`
`IPPH 100
`
`IPPH 471
`
`IPPH 562
`
`IPPH 587
`
`IPPH 521
`
`IPPH 690A
`
`PHAD 690
`
`IPPH 590
`
`PHRM 828
`
`PHRM 829
`
`PHRM 866
`
`AGRY 544
`
`Pharmaceutical Science Orientation
`
`Parenteral Products
`
`Manufacturing Processes
`
`Pharmaceutical Solids
`
`Drug Development
`
`Solids Discussion Group
`
`Introduction to Pharmaceutical Sciences Research
`
`Applied Thermodynamics
`
`Dosage Forms I
`
`Dosage Forms II
`
`Biotechnology and Advanced Parenterals
`
`Environmental Organic Chemistry
`
`2
`
`Instructor
`
`Instructor
`
`Instructor
`
`Instructor
`
`Guest Instructor
`
`Instructor
`
`Instructor
`
`Instructor
`
`Instructor
`
`Instructor
`
`Instructor
`
`Instructor
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 2 of 25
`
`

`

`Administration:
`
` Director of Graduate Studies. Academic advisor to new graduate students. Develop development
`program of individual graduate students in preparation to join a research group/advisor. Review and
`revise the Graduate Studies handbook for the department. 2016 – Present.
` Chair, Graduate Admissions Committee, Industrial and Physical Pharmacy. Evaluate application
`materials for students wanting to pursue a Ph.D. degree in the department. Conduct one-to-one
`interviews with applicants. Assess applicants’ scientific and academic qualifications for admission to
`the department. Vote on admission/non admission of student applicants. 2006 - 2016.
` Director, NSF-I/UCRC Dane O. Kildsig Center for Pharmaceutical Processing Research (CPPR).
`2005 – Present.
`Associate Director, Center for Pharmaceutical Processing Research (CPPR). 2004.
`
` Chair, Faculty Search Committee, Endowed Professorship, Department of Industrial and Physical
`Pharmacy. 2010.
`Assessment Committee, College of Pharmacy. 2010 – Present
`
` Graduate Fellowships Committee, 2004 – Present
`Faculty Council, 2012-2014
`
`SWOT (strengths, weaknesses, opportunities and threats) Analysis Task Force, 2014-2015
`
` University Grievances Committee, 2015 – 2018
`Professional Outcomes Task Force, 2015
`
` University Advisory Committee on Equity, 2017 - present
`
`Theses directed:
`
`Chen Mao, Ph.D. 2006. Structural relaxation and molecular mobility in organic amorphous pharmaceutical
`compounds. Purdue University.
`
`Fabrice Gusching, M.S. 2006. Antiplasticization of pharmaceutical polymers (Antiplasticisation des polymères
`à usage pharmaceutique), Univesité Louis Pasteur, Strasbourg, France. Co-advisor.
`
`François-Xavier Diringer, M.S. 2007. Influence of moisture on the ability of microcrystalline cellulose to form
`tablets. Univesité Louis Pasteur, Strasbourg, France. Co-advisor.
`
`Sai Prasanth Chamarthy, Ph.D. 2007. The different roles of suface and bulk effects on the functionality of
`pharmaceutical materials. Purdue University.
`
`Carole Bucher, M.S. 2008. Assessment of the distribution of API microparticles in polymeric films. Univesité
`Louis Pasteur, Strasbourg, France. Co-advisor.
`
`Michelle K. Papp, Ph.D. 2009. Application of acoustic emission to the monitoring of pharmaceutical unit
`operations. Purdue University
`
`Nathan A. Boersen, Ph.D. 2009. The development of roller compacted formulations using multivariate and
`dimensional analysis. Purdue University.
`
`Ji-Young Kim, Ph.D. 2009. Hydrotropic solubilization of poorly soluble drugs. Purdue University.
`
`Maria Elisa Luque. M.S. 2010. Toward the development of an ontological framework for drug-loaded film
`manufacture. Dept. of Chemical Engineering. Co-advisor.
`
`Ryan J. McCann. PhD. 2011. Investigating the density distribution of roller compacted ribbons. Purdue
`University.
`
`Andrew Otte, Ph.D 2011. From milling to particle engineering: formulations for dry powder inhalers.
`
`Xin Chen. PhD 2012. Solubility estimation and rapid structral characterization of small molecule drugs in
`polymers. Purdue University. Co-advisor.
`
`3
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 3 of 25
`
`

`

`Bo Zhou. PhD 2012. Development of laminate based, prefabricated dosage forms – Formulation, processing
`and characterization. Purdue University.
`
`Yan Zhang. Ph.D. 2012. Kinetic driving effects of phase transformations in mechanically activated powders.
`Purdue University.
`
`Kevin Boksa. PhD. 2014. Matrix-assisted cocrystallization: the simulataneous production and formulation of
`pharmaceutical cocrystals using melt extrusion. Purdue University.
`
`Yang Song. Ph.D. 2015. Acid-base interactions in amorphous solid dispersions: Formulation strategy for
`tyrosine kinase inhibitors. Purdue University. Co-Advisor.
`
`Jing Ling. Ph.D. 2017. Crystallization control using fabricated polymeric materials. Purdue University.
`
`Hwee Jing Ong. Ph.D. 2018. Drug solubilization by means of a surface-modified biopolymer enabled by hot
`melt extrusion. Purdue University.
`
`Mario Cano-Vega. 2019. Ph.D. Quality by Design approach to develop 3D Integrated Pharmaceuticals for
`personalized medicine. Purdue University. Co-Advisor.
`
`1999-2003
`1997-1999
`Pharm. and Anal. R&D
`Hoffmann-La Roche
`
`Research Leader (Solid-State Pharmaceutics)
`Principal Scientist (Solid-State Pharmaceutics)
`
`Physical characterization of solids and Particle Technology. Supervisory responsibility for the group’s
`activities and capabilities: X-ray powder diffraction, DSC and hot stage microscopy, TGA/IR, SEM, Image
`Analysis, particle size by Laser diffraction and Dynamic Light Scattering, Hygroscopicity (microbalance),
`Microcalorimetry (TAM), BET gas adsorption and gas pycnometry.
`
`the measurement and monitoring of physical
`identifying and devising methods for
`Responsible for
`properties/parameters critical for the development of a given specific product or process. Responsibilities
`include the physical characterization of active ingredients, final dosage forms and intermediate blends. Work
`with formulation and process development scientists in troubleshooting powder technology issues of
`processability such as flowability, granulation and dissolution during development and technology transfer.
`
`Leader of the Integrated Solid-State Strategy Team among international development centers for various
`projects. Designed and instituted methodology necessary for evaluating the physical attributes and stability
`for an amorphous formulation technology used in clinical trials. Work with Chemical Synthesis designing and
`implementing crystal polymorph screening strategy for new chemical entities during preclinical development
`and Kilo-lab production. Responsible for writing the IND and NDA sections on crystal polymorphism.
`Provide official characterization data to Analytical groups on drug substances and formulations for GLP and
`cGMP qualification. Responsible for the regulatory compliance of the Solid State Pharmaceutics laboratory.
`Responsible for the development and validation of physical testing methods for regulatory submission and
`transfer to Quality Management for testing during production. Responsible, in the capacity of System Owner,
`for
`the Computer System Validation plan and implementation as dictated by 21CFR Part 11 for
`instrumentation in the Solid State Pharmaceutics Laboratory. Technical Team Leader for preclinical activities
`(CMC section) of international project. Coordinate activities among scientists in the U.S., Germany and
`Switzerland,
`integrating Discovery Pharmacology, chemical supply,
`formulation and manufacturing,
`Toxicology and Pharmacokinetics.
`
`4
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 4 of 25
`
`

`

`Principal Scientist
`Sterile Dosage Forms
`
`1993-1997
`Pharmaceutical R&D
`Hoffmann-La Roche
`Developed injectable formulations for Phase 00 and Phase 0 studies. Worked in the solubilization and
`formulation of organic molecules to support Drug Discovery, early Toxicology and Pharmacokinetics.
`Setup the capability for injectable emulsion technology in the group to support proof-of-concept efforts in
`Discovery.
`
`Specific assignments: Parenteral development team leader for a polypeptide molecule in Phase II/III.
`Formulation research and GLP manufacture, compatibility testing with manufacturing process/materials.
`Formulation development and manufacture of IND-enabling stability lots, issue Directions for Manufacture
`of cGMP clinical lots and complete transfer to clinical supplies manufacturing area. Coordinate clinical
`supply manufacturing and analytical (stability, release, and cleaning assessment) activities with CMC
`leader for regulatory submissions and shipment to the clinic.
`Formulation scientist responsible for small molecule, line extension product. Manufacture of ANDA-
`enabling stability lots. Primary container selection studies, stopper extractables,
`tubing and filter
`membrane compatibility studies. Development of a manufacturing process suitable for
`trade lots.
`Preparation of Research Directions for technology transfer, scale-up and manufacture of exhibit lots.
`International Team Leader for project focused on the identification and evaluation of new technologies for
`drug delivery and drug development.
`
`1991-1993
`1990-1991
`Pharmaceutical R&D
`Hoffmann-La Roche
`
`Senior Scientist (Preformulation)
`Research Associate (Preformulation)
`
`Physicochemical characterization of new drug candidates. Development of stability-indicating methods,
`HPLC, TLC, UV/IR and Fluorescence spectra. Stability screening in solution and solid state, pH-solubility
`profile, pH-stability profile and kinetics, pKa determination.
`Photodegradation and drug-excipient
`compatibility studies, accelerated stability. Solubility/solubilization and partitioning studies. Developed a
`method for measuring partition coefficients using solid phase extraction.
`
`Also responsible for studies intended to address issues specific to discovery or development programs:
`QSAR studies to support drug discovery, studies on drug sorption to valve-gaskets to support aerosol
`development, compaction studies to support solid-dosage form formulation.
`
`1988-1990
`Soil Science Department
`University of Florida
`Gainesville, Florida
`
`Post-Doctoral Research Associate
`(Research on the fate and transport of organic compounds in complex
`mixtures)
`
`Responsible for all major technical aspects of the project: designing and conducting experiments, planning
`of future work, preparing and presenting progress reports to the sponsoring agency.
`
`Analytical (HPLC) method development, chemical and scintillation counting analyses in multi-component,
`multi-phasic matrices, extensive measurements of solubility/partitioning in miscible and immiscible solvent
`mixtures, and of sorption/partitioning to natural and synthetic polymers.
`Computer modeling of data; developed and published a model to predict solubility of organic compounds
`in non-ideal solvent mixtures.
`
`5
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 5 of 25
`
`

`

`1985-1988
`College of Pharmacy
`University of Arizona
`
`Graduate Research Assistant
`
`Graduate research on the theoretical and practical aspects of solubility and solubilization. Study of the
`relationship between chemical structure and the physicochemical properties of organic molecules in
`solution. Measurement of solubility and solubilization profiles in pure and mixed solvents. Extensive use of
`QSAR (Quantitative Structure-Activity Relationships) techniques including computer programming for
`modeling, computer data management, statistical analysis, and report generation.
`
`1984-1985
`College of Pharmacy
`University of Arizona
`
`Graduate Teaching Assistant
`
`Teaching Pharmaceutics laboratory to undergraduates. Preparation of short introductory lecture for each
`session. Guiding students through the experimental exercise. Reviewing and grading students’
`formulated product for appearance, yield and labeling. Reviewing pre-session homework assignments,
`preparing and grading laboratory tests.
`
`1981-1982
`Section of Microbiology
`National Univ. of Mexico
`
`Laboratory Assistant
`
`Preparing (compounding, filling and sterilizing) all necessary culture media for undergraduate Microbiology
`laboratory sessions. Preparing dyes used for visualization/identification of bacteria. Maintaining stock of
`sterilized glassware and materials needed for laboratory sessions.
`
`EDUCATION:
`
`1984-1988
`
`Ph.D. in Pharmaceutical Sciences
`Minor: Physical Chemistry
`University of Arizona
`Dissertation: Estimation of Aqueous Solubility of Organic Compounds.
`
`1983
`
`Internship: National General Hospital, Mexico and National University of Mexico
`
`1978-1982
`
`B.S. in Pharmaceutical chemistry
`National University of Mexico
`Mexico City, Mexico
`
`PROFESSIONAL MEMBERSHIPS:
`
`American Chemical Society
`American Association of Pharmaceutical Scientists
`
`DISTINCTIONS AND AWARDS:
`
`Peer Recognition Respiratory Drug Delivery VI, Virginia Commonwealth University, p. 284 (1998). J. Pharm.
`Sci., 83, p. 1216 (1994); Pharm. Tech., 18, p. 159, (1994). “Water Solubility. Methods of
`Estimation for Organic Compounds” by S. H. Yalkowsky and S. Banerjee. Marcel Dekker,
`1991.
`
`6
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 6 of 25
`
`

`

`1983
`
`1987
`
`1990
`
`1995
`
`1996
`
`1997
`
`1999
`
`Diploma: Third highest undergraduate GPA
`National University of Mexico.
`
`Rho Chi Honor Society
`University of Arizona, Tucson, Arizona.
`
`Project Reviewer
`Electric Power Research Institute, Palo Alto, CA.
`
`Special Recognition Bonus: Departmental coordinator for Preclinical Development
`redesign.
`
`Management Incentive Bonus
`
`Recognition Award for 1996
`Special Recognition Award for International Team Leader work
`
`Recognition award for characterization work on novel amorphous formulation
`
`2000-2002
`
`Land-O-Lakes Pharmaceutical Conference planning committee member
`
`2003
`
`2003
`
`2004
`
`2004
`
`2005
`
`2005
`
`2006
`
`2006
`
`2007
`
`2007
`
`2007
`
`2008
`
`Chair
`Land-O-Lakes Pharmaceutical Conference
`University of Wisconsin
`Theme: Molecular Pharmaceutics
`
`Silver Award
`Roche Research Olympiad
`For contribution on Integrated Drug Development work
`
`Associate Director
`Center for Pharmaceutical Processing Research (CPPR)
`Purdue University
`
`Purdue Research Foundation Fellowship. “Applications of hot-melt extrusion to the
`production of drug dispersions with improved drug delivery attributes for poorly soluble
`drugs.” (Sai Chamarthy)
`
`Director
`Dane O. Kildsig Center for Pharmaceutical Processing Research (CPPR)
`Purdue University
`
`Arden House Pharmaceutical Conference. Planning committee. Pharmaceutical
`Materials Science
`
`Proposal Reviewer
`National Science Foundation
`
`Seed for Success Award. Purdue University.
`
`Seed for Success Award. Purdue University.
`
`Schering-Plough Science & Innovation Award (Sai Chamarthy)
`
`Bisland Doctoral Fellowship (Sai Chamarthy)
`
`Book proposal reviewer. Wiley Books.
`
`7
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 7 of 25
`
`

`

`2008
`
`2008
`
`2008
`
`Jenkins-Knevel Award for Outstanding Graduate Research (Michelle Papp)
`
`Lieberman Award for an outstanding graduate student in Industrial and Physical
`Pharmacy (Ryan McCann)
`
`Dean’s Medal for distinguished service. Faculty of Pharmacy. Louis Pasteur University,
`Strasbourg, France.
`
`2008-2010
`
`Proposal Reviewer. National Science Foundation
`
`2009
`
`2010
`
`2010
`
`2010
`
`2010
`
`2012
`
`2012
`
`2013
`
`Entrepreneurial Leadership Academy Fellow. Purdue University
`
`Session Chair, Thermo-Mechanical Response of Molecular Solids: Multi-Resolution
`Theory, Simulations, and Experiments: Molecular Solids I. TMS 2010. 139th Annual
`Meeting and Exposition, The Minerals, Metals & Materials Society, Seattle, Washington.
`
`Faculty Awards of Excellence. Team Award, Pharmaceutical Engineering Research
`Team. Purdue University.
`
`Top Reviewer Recognition. Journal of Pharmaceutical Sciences
`
`PREPP - Purdue Realization and Entrepreneurship Postdoctoral and Doctoral Program
`(Andrew Otte, Ph.D.)
`
`Winner. “Come and dine with an Editor” competition. International Journal of
`Pharmaceutics. Chicago, Illinois.
`
`Innovation and Commercialization Center. Success Stories. Purdue University. Featured
`article
`
`Session Chair, 15th International Workshop on the Physical Characterization of
`Pharmaceutical Solids, Philadelphia, Pennsylvania.
`
`2013-2014
`
`Discovery Park Fellow, Bindley Biosciences Center, Purdue University. 3D Integrated
`Pharmaceuticals - Large Area Web Nanomanufacturing methods and preliminary testing.
`
`2014
`
`2014
`
`2015
`
`2015
`
`National Science Foundation I-Corps, Technology Selected.
`
`Innovators Hall of Fame Inductee, Purdue University.
`
`Outstanding Advisor. Purdue University Student Soybean Product Innovation. Indiana
`Soybean Alliance.
`
`Lieberman Book Award for outstanding graduate student (Hwee Jing Ong). Purdue
`University.
`
`2016 - present
`
`Purdue University Senate
`
`2016
`
`2017
`
`2017
`
`First place team (scientific advisor). Exfoliant for Use as Replacement for Plastic
`Microbeads. Purdue University Student Soybean Product Innovation. Indiana Soybean
`Alliance.
`
`IPEC Excipient Graduate Student Award (Carolina Mora, Ph.D. program). International
`Pharmaceutical Excipients Council of the Americas Foundation
`
`Graduate Student Research Award (Hwee Jing Ong). American Association of Indian
`Pharmaceutical Scientists
`
`8
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 8 of 25
`
`

`

`2017
`
`2019
`
`2020
`
`Chair. Patient-Centric Focus Group. American Association of Pharmaceutical Scientists
`
`Session Chair. Indiana Summit 2019. Vellore Institute of Technology, Indiana University-
`Purdue University (IUPUI), Indianapolis, Indiana.
`
`People’s Choice Award. Team scientific advisor. Non-Toxic, Biodegradable Filament for
`Use in 3D Printing. Purdue University Student Soybean Product Innovation. Indiana
`Soybean Alliance.
`
`JOURNAL REVIEWER:
`
`ACS Omega
`AAPS PharmSciTech
`Analytical Chemistry Letters
`Analytical Methods
`Chemosphere
`Colloids and Surfaces A
`Critical Reviews in Environmental Science and Technology
`Critical Reviews in Therapeutic Drug Carrier Systems
`Crystal Growth and Design
`Current Opinion in Food Science
`Drug Development and Industrial Pharmacy
`Environmental Science and Technology
`European Journal of Pharmaceutics and Biopharmaceutics
`Expert Opinion on Drug Delivery
`Industrial & Engineering Chemistry Research
`International Journal of Biological Macromolecules
`International Journal of Pharmaceutics
`Journal of Chemical and Engineering Data
`Journal of Chemical Physics
`Journal of Food and Agricultural Sciences
`Journal of Controlled Release
`
`PUBLICATIONS:
`
`Journal of Pharmaceutical Innovation
`Journal of Pharmaceutical Sciences
`Journal of Physical Chemistry
`Journal of Thermal Analysis and Calorimetry
`Journal of Solution Chemistry
`Journal of the Air and Waste Management Association
`Materials
`Materials Chemistry and Physics
`Medicinal Chemistry Letters
`Metallurgical and Materials Transactions A
`Molecular Pharmaceutics
`Molecules
`Pharmaceutical Development and Technology
`Pharmaceutical Research
`Pharmaceutics
`Pharmacy
`Physical Chemistry Chemical Physics
`Polymer
`Powder Technology
`Spectrochimica Acta
`Thermochimica Acta
`
`R. Pinal and M.T. Carvajal. Integrating Particle Microstructure, Surface and Mechanical Characterization with Bulk
`Powder Processing. KONA Powd. Part. J. 37, 195-213 (2020).
`
`D. Cebeci-Maltaş, R. Pinal, L. Taylor and D. Ben-Amotz, Spatial light modulators as PAT sensors: Raman applications.
`Eur. Pharm. Rev. 23, 72-74 (2018).
`
`T. Marín, P. Montoya, O. Arnache, R. Pinal, J. Calderón. Bioactive films of zein/magnetite magnetically stimuli-
`responsive for controlled drug release. J. Magn. Magn. Mater. 458, 355-364 (2018).
`
`H. J. Ong and R. Pinal. Drug solubilization by means of a surface-modified edible biopolymer enabled by hot melt
`extrusion. J. Pharm. Sci. 107, 402-411 (2018).
`
`P. Myrdal, K. Morris, R. Pinal, N. Jain, P.L.D. Wildfong and G. Zografi. Professor Samuel H. Yalkowsky: Scientist,
`mentor, and molecular empath. J. Pharm. Sci. 107, 2-4 (2018).
`
`D. Cebeci-Maltaş, D. Ben-Amotz, M. A. Alam, P. Wang and R. Pinal. Photobleaching profile of Raman peaks and
`fluorescence background. Eur. Pharm. Rev. Issue 6 (2017).
`
`Y. Song, D. Zemlyanov, X. Chen, Z. Su, H. Nie, J.W. Lubach, D.Smith, S. Byrn and R. Pinal. Acid-base interactions in
`amorphous solid dispersions of lumefantrine prepared by spray-drying and hot-melt extrusion using X-ray photoelectron
`spectroscopy. Int. J. Pharm. 514, 456-464 (2016).
`
`9
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 9 of 25
`
`

`

`E.A Münchow, H.J. Hammann, M.T, Carvajal, R. Pinal, and M.C. Bottino. Stain removal effect of novel papain- and
`bromelain-containing gels applied to enamel. Clin. Oral Invest. 20, 2315–2320 (2016).
`
`N. Boersen, D. Belair, G. E. Peck, and R. Pinal. A dimensionless variable for the scale up and transfer of a roller
`compaction formulation. Drug Dev. Ind. Pharm. 42, 60-69 (2016).
`
`N. Boersen, M. T. Carvajal, K. R. Morris, G. E. Peck, and R. Pinal. The influence of API concentration on the roller
`compaction process: Modeling and prediction of the post compacted ribbon, granule and tablet properties using
`multivariate data analysis. Drug Dev. Ind. Pharm. 41, 1470-1478 (2015).
`
`M. F. Hamilton, A. D. Otte, R. L. Gregory, R. Pinal, A. Ferreira-Zandoná and M. C. Bottino. Physico-mechanical and
`antibacterial properties of experimental resin-based dental sealants modified with nylon-6 and chitosan nanofibers. J.
`Biomed. Mat. Res. B Appl. Biomat. 103, 1560–1568 (2015).
`
`A. J. Harrison, A. Otte, T. Carvajal, R. Pinal, S. P. Beaudoin. Cohesive hamaker constants and dispersive surface
`energies of RDX, PETN, TNT, and ammonium nitrate-based explosives. Prop. Explos. Pyrotech., 40, 892–897 (2015).
`
`X. Chen, H. M. Fadda, A. Aburub, D. Mishra and R. Pinal. Cosolvency approach for assessing the solubility of drugs in
`poly(vinylpyrrolidone). Int. J. Pharm. 494, 346-356 (2015).
`
`N. Boersen, M. T. Carvajal, K. R. Morris, G. E. Peck, and R. Pinal. The influence of API concentration on the roller
`compaction process: modeling and prediction of the post compacted ribbon, granule and tablet properties using
`multivariate data analysis. Drug Dev. Ind. Pharm. 41, 1470-1478 (2015).
`
`L. Zhang, A. D. Otte, M. Xiang, D. Liu, Rodolfo Pinal. Investigation of film with -galactosidase designed for stabilization
`and handling in dry configuration Molecules, 20, 17180-17193 (2015).
`
`W. Yu, R. Rahimi, M. Ochoa, R. Pinal, and B. Ziaie. A smart capsule with GI-tract-location-specific payload release.
`IEEE Trans. Biomed. Eng. 62, 2289-2295 (2015).
`
`K. Boksa, A. Otte and R. Pinal. Matrix-assisted cocrystallization: The simultaneous production and formulation of
`pharmaceutical cocrystals by hot-melt extrusion. J. Pharm. Sci. 103, 2904-2910 (2014).
`
`H. M. Fadda, X. Chen, A. Aburub, D. Mishra and R. Pinal. A novel method for determining the solubility of small
`molecules in aqueous media and polymer solvent systems using solution calorimetry. Pharm. Res. 31, 1735-1743
`(2014).
`
`D. Cebeci-Maltas, R. McCann, P. Wang, R. Pinal, R. Romanach and D. Ben-Amotz. Pharmaceutical application of fast
`Raman hyperspectral imaging with compressive detection strategy. J. Pharm. Innov. 9, 1-4 (2014).
`
`S. Janaswamya, K.L. Gill, O.H. Campanella and R. Pinal. Organized polysaccharide fibers as stable drug carriers.
`Carbohyd. Polym. 94, 209-215 (2013).
`
`E. H. Lee, S. Byrn, and R. Pinal. The solution properties of mefenamic acid and a closely related analogue are
`indistinguishable in polar solvents but significantly different in nonpolar environments. J. Pharm. Sci. 101, 4529-4539
`(2012).
`
`N. Shah, H. Sandhu, W. Phuapradit, R. Pinal, R. Iyer, A. Albano, A. Chatterji, S. Anand, D.-S. Choi, K. Tang, H. Tian, H.
`Chokshi, D. Singhal, and W. Malick. Development of novel microprecipitated bulk powder (MBP) technology for
`manufacturing stable amorphous formulations of poorly soluble drugs. Int. J. Pharm. 438, 53-60 (2012).
`
`A. Otte, Y. Zhang, M. T. Carvajal, and R. Pinal. Milling induces disorder in crystalline griseofulvin and order in its
`amorphous counterpart. CrystEngComm 14, 2560-2570 (2012).
`
`P. Wang, M. N. Slipchenko, B. Zhou, R. Pinal, and J. Cheng. Mechanisms of epi-detected stimulated Raman scattering
`microscopy. IEEE J. Sel. Topics Quant. Electron. 18, 384-388 (2012).
`
`10
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 10 of 25
`
`

`

`M. Thommes, D. R. Ely, M. T. Carvajal and R. Pinal. Improvement of the dissolution rate of poorly soluble drugs by solid
`crystal suspensions. Mol. Pharmaceutics 8: 727-735 (2011).
`
`A. Zarow, B. Zhou, X. Wang, R. Pinal and Z. Iqbal. Spectroscopic and X-ray diffraction study of structural disorder in
`cryomilled and amorphous griseofulvin. Appl. Spectroscopy 65, 135-143 (2010).
`
`J.-Y. Kim, S. Kim, M. Papp, K. Park, and R. Pinal. Hydrotropic solubilization of poorly water-soluble drugs. J. Pharm.
`Sci., 99, 3953-3965 (2010).
`
`Y. Miyako, N. Khalef, K. Matsuzaki, and R. Pinal. Solubility enhancement of hydrophobic compounds by cosolvents:
`Role of solute hydrophobicity on the solubilization effect. Int. J. Pharm., 393, 48-54 (2010).
`
`C. Mao, S. P. Chamarthy, S. R. Byrn, and R. Pinal. Theoretical and experimental considerations on the enthalpic
`relaxation of organic glasses using differential scanning calorimetry. J. Phys. Chem. B, 114, 269–279 (2010).
`
`N. Khalef, R. Pinal, and A. Bakri. Limitations of amorphous content quantification by isothermal calorimetry using
`saturated salt solutions to control relative humidity: alternative methods. J. Pharm. Sci., 99, 2080-2089 (2010).
`
`S. P. Chamarthy, N. Khalef, N. Trasi, A. Bakri, M. T. Carvajal, and R. Pinal. The effect of dehydration conditions on the
`functionality of anhydrous amorphous raffinose. Eur. J. Pharm. Sci., 40, 171-178 (2010).
`
`Y. Miyako, Y. Zhao, K. Takeshima, T. Kataoka, T. Handa, and R. Pinal. Solubility of hydrophobic compounds in water–
`cosolvent mixtures: relation of solubility with water–cosolvent interactions. J. Pharm. Sci., 99, 293-302 (2009).
`
`S. P. Chamarthy, R. Pinal, and M. T. Carvajal. Elucidating raw material variability - Importance of surface properties and
`functionality in pharmaceutical powders. AAPS PharmSciTech, 10, 780-788 (2009).
`
`J.L.P. Soh, F. Wang, N. Boersen, R. Pinal, G.E. Peck, M.T. Carvajal, J. Cheney, H. Valthorsson, and J. Pazdan. Utility
`of multivariate analysis in modeling the effects of raw material properties and operating parameters on granule and
`ribbon properties prepared in roller compaction. Drug Dev. Ind. Pharm. 34, 1022-1035 (2008).
`
`S.P. Chamarthy and R. Pinal. The nature of crystal disorder in milled pharmaceutical materials. Colloids Surf. A, 331,
`68-75 (2008).
`
`S. P. Chamarthy and R. Pinal. Plasticizer concentration and the performance of polymeric drug delivery systems.
`Colloids Surf. A, 331, 25-30 (2008).
`
`R. Pinal. Entropy of mixing and the glass transition of amorphous mixtures. Entropy, 10, 207-223 (2008).
`
`T. Feng, F. Wang, R. Pinal, C. Wassgren and M. T. Carvajal. Investigation of the variability of NIR in-line monitoring of
`roller compaction process by using Fast Fourier Transform (FFT) analysis. AAPS Pharm SciTech, 90, 419-424 (2008).
`
`M. Papp, C. P. Pujara, and R. Pinal. Monitoring of high-shear granulation using acoustic emission: Predicting granule
`properties. J. Pharm. Innov. 3, 113-122 (2008).
`
`Y. Miyako, H. Tai, K. Ikeda, R. Kume and R. Pinal. Solubility screening on a series of structurally related compounds.
`Cosolvent-induced changes on the activity coefficient of hydrophobic solutes. Drug Dev. Ind. Pharm. 34, 499-505
`(2008).
`
`T. Feng, R. Pinal and M.T. Carvajal. Process induced disorder in crystalline materials: differentiating defective crystals
`from the amorphous form of griseofulvin. J. Pharm. Sci., 97, 3207-3221 (2008).
`
`J. L. P. Soh, N. Boersen, M. T. Carvajal, K. R. Morris, G. E. Peck and R. Pinal. Importance of raw material attributes for
`modeling ribbon and granule properties in roller compaction: Multivariate analysis on roll gap and NIR spectral slope as
`process critical control parameters. J. Pharm. Innov., 2, 106-124 (2007).
`
`C. Mao, S. P. Chamarthy and R. Pinal. Calorimetric study and modeling of molecular mobility in amorphous organic
`pharmaceutical compounds using a modified Adam-Gibbs approach. J. Phys. Chem. B. 111, 13243-13252 (2007).
`
`11
`
`IPR2020-00769
`United Therapeutics EX2003
`Page 11 of 25
`
`

`

`S. P. Chamarthy and R. Pinal. Moisture induced antiplasticization in microcrystalline cellulose compacts. Tablets and
`Capsules, 5, 22-33 (2007).
`
`C. Mao, S. P. Chamarthy S.R. Byrn and R. Pinal. Time-dependence of molecular mobility during structural relaxation
`and its impact on organic amorphous solids: an investigation based on a calorimetric approach. Pharm. Res. 23, 1906-
`1917 (2006).
`
`C. Mao, S. P. Chamarthy and R. Pinal. A calorimetric method to estimate molecular mobility of amorphous solids at
`relatively low temperatures. Pharm. Res. 23, 1906-1917 (2006).
`
`M.T. Carvajal, S.P. Chamarthy, A. Otte, and R. Pinal. Influence Of Residual Water on the Surface Functionality of
`Powdered Materials, In Proceedings of Respiratory Drug Delivery X (2006), Richard N. Dalby, Peter R. Byron, and J.
`Peart, eds., Interpharm Press, Buffalo Grove, Illinois. p. 757-760.
`
`Z. Qiu, J.G. Stowell, K.R. Morris, S.R. Byrn and R. Pinal. Kinetic study of the Maillard reaction between metoclopramide
`hydrochlor